Effects of cocoa on altered metabolite levels in purine metabolism pathways and urea cycle in Alzheimer's disease in C. elegans

Dietary interventions have gained much attention as alternative therapies in aging-associated diseases. Epidemiological studies suggest that polyphenols (PPs) play an important role in this regard. Cocoa is rich in PPs, greater in amount than in teas and red wine. This study aimed to characterize the age-associated and amyloid-β (Aβ)-induced changes in metabolism in C. elegans and the effects of cocoa supplementation. An untargeted Gas Chromatography-Mass Spectrometry (GC-MS) approach was used to determine the changes in endogenous metabolite levels in wild-type and a transgenic C. elegans strain expressing pan-neuronal Aβ (GRU102). Aging appeared to alter some amino acid levels in C. elegans. Cocoa supplementation reduced leucine and tyrosine levels in old age (day 12). GRU102 showed higher proline and asparagine relative to control worms at a young age (day 4) which may have a connection with cognitive deficits in Alzheimer's disease (AD). Cocoa reduced the elevated levels of these two amino acids to the levels in the control worms. The purine derivative, hypoxanthine was higher in GRU102 relative to the control worms at their middle age (day 8) where the elevated are known to contribute to memory deficits in AD. Cocoa supplementation reduced the elevated hypoxanthine to normal levels. Aβ expression showed alterations in the urea cycle in worms in their middle age as indicated by increased ornithine.